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DNA Methylation and the Expression of IL-4 and IFN-γ Promoter Genes in Patients with Bronchial Asthma

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Abstract

Although CpG methylation is thought to be a negative regulator of gene transcription, its relationship with cytokine expression remains unclear. Interleukin (IL)-4 and interferon (IFN)-γ are major cytokines that affect the differentiation of naïve CD4+ T lymphocytes into the Th1 and Th2 lineage. We used bisulfite deoxyribonucleic acid modification and sequencing to examine the relationship between CpG methylation and IL-4 and IFN-γ gene expression before and after allergen stimulation in human CD4+ T lymphocytes from sensitized hosts. In naïve cells, the CpGs in the promoter regions were methylated largely in both the IL-4 and IFN-γ genes. After Dermatophagoides pteronyssinus/Dermatophagoides farinae stimulation, the degree of unmethylation in the IL-4 gene increased in cells from patients with bronchial asthma. After phytohemagglutinin stimulation, the degree of unmethylation increased in cells from nonallergic control subjects. The concentration of IL-4 was strongly correlated with the degree of unmethylation in the patient group. These data suggest that CpGs located at −80 of the IL-4 gene and at −295, −186, and +122 of the IFN-γ gene have regulatory activities important for cytokine expression. We conclude that the stimulation of CD4+ T lymphocytes causes considerable increases in the degree of unmethylation and that in sensitized hosts, the extent of unmethylation correlates with the concentration of IL-4.

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Acknowledgement

This study was sponsored by In-Sung Foundation for Medical Research.

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Authors and Affiliations

  1. Division of Allergies, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-Gu, Seoul, South Korea, 135-710

    Nam-Hee Kwon, Jin-Young Lee, Mi-Jung Oh & Dong-Chull Choi

  2. Genomic Research Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Jin-Seuk Kim

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  1. Nam-Hee Kwon
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  2. Jin-Seuk Kim
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Correspondence to Dong-Chull Choi.

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Kwon, NH., Kim, JS., Lee, JY. et al. DNA Methylation and the Expression of IL-4 and IFN-γ Promoter Genes in Patients with Bronchial Asthma. J Clin Immunol 28, 139–146 (2008). https://doi.org/10.1007/s10875-007-9148-1

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  • DOI: https://doi.org/10.1007/s10875-007-9148-1

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